The present invention is related to Fee, U.S. Pat. No. 6,377,619, issued Apr. 23, 2003, entitled xe2x80x9cPredictive Probe Stabilization Relative to Subject Movementxe2x80x9d, filed concurrently herewith and commonly assigned to Agere Systems, Inc. (formerly assigned to Lucent Technologies, Inc.), and incorporated by reference herein, with priority claimed for all commonly disclosed subject matter (the xe2x80x9crelated applicationxe2x80x9d).
1. Field of the Invention
The present invention relates, in general, to probe stabilization relative to movement of a subject. More particularly, the present invention relates to interferometric and active stabilization, of an intracellular probe, relative to the movement of the subject.
2. Background of the Invention
Much of our understanding of the function of the brain has come from probing the nervous system at the level of single neurons. With few exceptions, the study of single neurons in behaving animals has been limited to extracellular recordings of action potentials. Action potentials, however, represent only the final, output state of a neuron whose response is essentially determined by the electrical and chemical interactions between smaller, functionally distinct neuronal compartments such as synapses, dendrites, and somata. Nearly all experimental information about the properties and behavior of neurons at this level comes from in-vitro and cell culture experiments. Furthermore, it is known that neuronal integration and firing properties are modulated by neuromodulatory influences and other activities. As a consequence, complete understanding of brain function ultimately requires observation of neuronal compartments and their interactions in intact, live and behaving subject animals.
Problems with mechanical stability make observations of neurons much more difficult in whole-animal preparations than in in-vitro or cell culture preparations. Many structures of interest in neurons are small (on the order of 1 to 10 microns in size), and because electrical and optical probes must be positioned near or inside the cell membrane to function, high quality and long lasting recordings require stable mechanical placement of the probe relative to the tissue. Drift or motion of the electrode or other probe relative to the recorded cell may interfere with good probe penetrations or seals on a neuron. Even when good penetration or seal is achieved, motion may also cause large variations in the recorded signals, degrade the health of the cell, and limit the duration of the recording.
Although a number studies have been published that involve intracellular recordings in anesthetized animals and even awake animals, brain motion makes intracellular recording difficult under even the best conditions. In all these experiments, the essential means of stabilizing the brain is to restrain the head of the animal with a stainless steel plate or pin secured to the cranium, potentially interfering with desired measurements. For example, such restraining systems do not allow for measurements in an active, moving subject, thereby limiting experimental measurements to non-active physiological states. Other methods, such as passive tracking of an electrode, may damage fragile brain tissue, or interfere with the subject under study and potentially affect the resulting measurements.
As a consequence, a need remains to provide a method and system for probe stabilization, relative to subject movement, to provide for accurate measurement within a live subject. The method and system should be active, and should accommodate gross or large-scale subject movement which may otherwise interfere with accurate measurements. In addition, the method and system should not alter or interfere with the physiological states of the subject, and should otherwise minimize contact with the subject tissue, to avoid interfering with the processes under study, to avoid tissue damage, and also to avoid other potential sources of error.
In accordance with the present invention, a method and system are provided for active probe stabilization, for accommodating subject movement which may otherwise interfere with accurate measurements. In addition, the method and system of the present invention do not alter or interfere with the physiological states of the subject, and otherwise minimizes contact with the subject tissue, to avoid interfering with the processes under study, to avoid tissue damage, and also to avoid other potential sources of error.
In the preferred method and system for active probe stabilization, a probe (such as a microelectrode) is mounted on a piezoelectric manipulator and inserted into the subject, so that the probe is moveable in response to a control voltage. A laser interferometer is utilized to generate a light beam and to split the light beam into first and second light beams. The interferometer is operable to transmit the first light beam to the subject and to receive a reflected light beam. The interferometer modulates the second light beam with a modulating signal, such as a 110 MHz radio frequency signal, to form a reference light beam. The interferometer then combines the reflected light beam and the reference beam to form an interference pattern.
A demodulator is coupled to the manipulator and to the interferometer. The demodulator provides the control voltage to the manipulator for probe movement. Using the interference pattern detected within the interferometer, the demodulator quadrature demodulates a phase shift of the modulating signal (RF signal) to determine a displacement signal. The displacement signal is proportional to the amount and direction of subject movement, and may be in increments of one-fourth of a wavelength of the laser light beams. The displacement signal may accommodate comparatively significant subject movements, on the order of 30-40 microns. The displacement signal is then converted to an analog form as the control voltage input into the manipulator.